143
144 10. Lung
Case 61
FIGURE 61A. Pap Stain: Transbronchial FNA of a lung lesion showing mostly isolated small cells with pyknotic nuclei. Differential diagnosis includes small cell carcinoma and lymphoma.
FIGURE 61B. Cytokeratin: Many cells show paranuclear punctate staining for cytokeratin.
Small Cell Carcinoma
Tips
The diagnosis of a small cell carcinoma is usually confi rmed by a positive cytokeratin staining; this excludes lymphomas. There is no need for includ- ing chromogranin and synaptophysin, because the former is expressed in less than 40% of small cell carcinomas and the latter may be expressed by nonsmall cell carcinomas.
Suggested Reading: 7
146 10. Lung
Case 62
FIGURE 62A. Pap Stain: Bronchial brushings from a 68-year-old male. Isolated small cells with hyperchromatic nuclei are seen; small cell carcinoma or malignant lymphoma.
FIGURE 62B. Cytokeratin: There is positive perinuclear reaction for cytokeratin.
Small Cell Carcinoma
Tips
Cytokeratin reaction in small cell carcinomas is either in the form of punc- tate paranuclear or perinuclear staining pattern. This case shows the latter.
Suggested Reading: 7
148 10. Lung
Case 63
FIGURE 63A. Pap Stain: Poorly differentiated nonsmall cell carcinoma in bronchial brushings. One can further characterize this tumor by immunocytochemistry.
FIGURE 63B. P63: Positive nuclear staining of tumor cells for p63 favors the diagnosis of squamous cell carcinoma.
Squamous Cell Carcinoma, Poorly Differentiated
Tips
• A combination of TTF-1 and p63 should help to subclassify most nonsmall cell carcinomas of the lung. TTF-1 is expressed by most adenocarcinomas but not by squamous cell carcinomas, while p63 is seen only in squamous cell carcinomas.
• In adenosquamous carcinomas of lung there may be focal staining for TTF-1 and p63 in the same tumor.
Suggested Reading: 45
150 10. Lung
Case 64
FIGURE 64A. Pap Stain: FNA of a peripheral lung tumor in a 71-year-old female.
The morphology is suggestive of squamous cell carcinoma.
FIGURE 64B. TTF-1: Tumor Cells show positive nuclear reaction for TTF-1. This favors the diagnosis of adenocarcinoma.
Adenocarcinoma of the Lung
Tips
• A combination of TTF-1 and p63 should help to subclassify most nonsmall cell carcinomas of the lung. TTF-1 is expressed by most adenocarcinomas but not by squamous cell carcinomas, while p63 is seen only in squamous cell carcinomas.
• In adenosquamous carcinomas of lung there may be focal staining for TTF-1 and p63 in the same tumor.
Suggested Reading: 45, 47, 48
152 10. Lung
Case 65
FIGURE 65A. Pap Stain: FNA of lung in a 55-year-old male. There is a cluster of small cells with ill-defi ned cytoplasms and a small group of larger cells with eosino- philic cytoplasms (upper right).
FIGURE 65B. P63: Positive reaction for p63 in the cells with eosinophilic cyto- plasms supports their squamous differentiation. The small cell component remains negative.
Small Cell Carcinoma with Focal Squamous Differentiation
Tips
Small cell carcinomas of the lung do not stain for p63 unless they have focal squamous differentiation. Therefore, p63 is a good marker to separate positive basaloid squamous cell carcinomas from the negative small cell carcinomas.
Suggested Reading: 7
154 10. Lung
Case 66
FIGURE 66A. Pap Stain: FNA of lung in a 66-year-old female. Nonsmall cell car- cinoma is favored, but a metastasis cannot be excluded.
FIGURE 66B. TTF-1: Tumor cells are positive for TTF-1, supporting their pulmo- nary origin.
Adenocarcinoma of the Lung
Tips
The only other possibility in this case is a TTF-1 pasitive metastatic thyroid carcinoma. Thyroglobulin should be used if that possibility is entertained.
Suggested Reading: 46
156 10. Lung
Case 67
FIGURE 67A. Pap Stain: FNA of lung in a patient with a history of bronchioloal- veolar carcinoma of the contralateral lung. Is it an adenocarcinoma or a squamous cell carcinoma?
FIGURE 67B. TTF-1: Tumor cells are positive for TTF-1.
Adenocarcinoma; Bronchioloalveolar by History
Tips
Most bronchioloalveolar carcinomas of the lung, with the exception of intestinal-type mucinous variants, are positive for TTF-1. Those tumors may also be positive for CK20 and CDX-2 and, hence, their differentiation from metastatic colonic carcinomas may be diffi cult.
Suggested Reading: 46, 47
158 10. Lung
Case 68
FIGURE 68A. Pap Stain: FNA of lung in a 76-year-old male with history of colonic carcinoma. The cytomorphology is suggestive of an adenocarcinoma.
FIGURE 68B. CK20: Tumor cells are negative for CK20.
FIGURE 68C. CK7: Positive reaction for CK7 is seen in most tumor cells.
Diagnosis
Adenocarcinoma of the Lung
Tips
• When the differential diagnosis is between a primary lung adenocarcinoma and a metastatic colonic adenocarcinoma, a combination of CK20 and CK7 will be helpful as lung adenocarcinomas are usually positive for CK7 and negative for CK20.
• TTF-1 is also helpful (48).
Suggested Reading: 48
160 10. Lung
Case 69
FIGURE 69A. Pap Stain: FNA of a solitary lung nodule in 63-year-old male with a history of colonic carcinoma.
FIGURE 69B. CK20: Tumor cells are positive for CK20.
FIGURE 69C. CDX-2: They are also positive for CDX-2.
Diagnosis
Metastatic Adenocarcinoma of the Colon
Tips
When adenocarcinoma of colon is suspected, CDX-2 can be used in addi- tion to CK20 as a marker for the colon. CDX-2 positivity alone, however, is not specifi c for colonic carcinomas.
Suggested Reading: 28
162 10. Lung
Case 70
FIGURE 70A. Pap Stain: FNA of a lung in a female patient with a history of mammary carcinoma. Cytology is consistent with a mucinous adenocarcinoma.
FIGURE 70B. Estrogen Receptor (ER): Tumor cells are uniformly positive for ER.
Metastatic Mammary Carcinoma
Tips
• When monoclonal antibody ER-ID5 is used, only mammary and gynecologic cancers stain positively. This is not the case when other ER antibodies, such as 6F11 are used. The latter frequently stains lung, thyroid, and other nonbreast, nongynecologic cancers. For that reason, we only use ER-ID5 antibody.
• The pattern of ER-1D5 staining in breast cancer is usually diffuse, whereas in gynecologic tumors it is expressed focally.
Suggested Reading: 49
164 10. Lung
Case 71
FIGURE 71A. Pap Stain: FNA of a peripheral pulmonary nodule. The bland cytomorphology is suggestive of a carcinoid tumor.
FIGURE 71B. Chromogranin: All tumor cells are positive for chromogranin.
Pulmonary Carcinoid
Tips
Most carcinoids of the lung express chromogranin. Staining for individual peptide hormones in these tumors however, is less rewarding. The differ- ential diagnosis between a pulmonary carcinoid and a small cell carcinoma cannot be resclved by ICC. Cytologically, small cell corcinomas may show necrosis, chromatin streaking, and so on. The clinical information and X- ray fi ndings may also be helpful.
Suggested Reading: 50
166 10. Lung
Case 72
FIGURE 72A. Pap Stain: FNA of peripheral lung lesion. There are loosely cohe- sive cells with pleomorphic nuclei. A neuroendocrine tumor is in the differential diagnosis.
FIGURE 72B. Chromogranin: Strong cytoplasmic staining for chromogranin sup- ports the morphologic impression of a neuroendocrine neoplasm.
Pulmonary Carcinoid
Tips
The differentical diagnosis between a pulmonary carcinoid and a small cell carcinoma cannot be resolved by ICC. Cytologically, small cell carcinomas may show necrosis, chromatin streaking, and so on. The clinical informa- tion and X-ray fi ndings may be helpful.
Suggested Reading: 50
